Alterations of Smad expression and activation in defining 2 subtypes of human head and neck squamous cell carcinoma.

Abstract

We postulated that disruptions of the canonical transforming growth factor-beta (TGF-β)/Smad signaling pathway might contribute to the development of head and neck squamous cell carcinoma (HNSCC). A cohort of 798 HNSCC tumor samples from 346 patients were analyzed by immunohistochemistry (IHC) to define the pattern of expression of (phospho)Smad2, (phospho)Smad3, and Smad4. We found that 19%, 40%, and 12% of HNSCC specimens failed to express pSmad2, pSmad3, or Smad4, respectively. Loss of Smad2/3 activation was observed in 8.5% of specimens. In addition, 4% of specimens failed to express only Smad4. Moreover, patients with pSmad2/3-negative tumors had a significantly better overall survival than that of those whose tumors expressed activated Smad2/3. In contrast, loss of Smad4 expression did not have prognostic significance. Our results indicate that HNSCC in which Smad2/3 are inactivated or in which Smad4 expression is lost represent 2 distinct tumor subtypes with different clinical outcomes.